Diazepinone derivatives

A method for the treatment of a substance-related disorder through mGluR5 antagonism comprising administration of a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof to a patient in need of treatment thereof

• wherein
• A is a fused five- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur;
• R1 is —X2—B2;
• X2 is bond or C1-3alkylene, wherein one carbon atom of the C1-3alkylene may be replaced by a group selected from carbonyl;
• oxygen;
• sulfur;
• —S(O)—;
• —S(O)2—;
• amino, which may be substituted by C1-4alkyl;
• —NH—C(O)—;
• —C(O)—NH—;
• —C(O)—O—;
• —O—C(O)—;
• —NH—S(O)2—;
• —S(O)2—NH—;
• and —NHC(O)NH—;
• B2 is a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R6;
• each R6 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy;
• or two R6 at the same ring atom together are oxo;
• m is 0, 1, 2, 3 or 4;
• each R2 independently is halogen, cyano, hydroxy, amino, C1-4alkyl;
• C1-4halogenalkyl;
• C1-4hydroxyalkyl;
• C1-4aminoalkyl;
• C1-4alkylamino-C1-4alkyl;
• di-(C1-4alkyl)amino-C1-4alkyl;
• C1-4alkoxy-C1-4alkyl;
• C2-4alkenyl;
• C2-4halogenalkenyl;
• C2-4alkinyl;
• C2-4halogenalkinyl;
• C1-4alkoxy;
• C1-4halogenalkoxy;
• C1-4alkyl-amino;
• di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;
• n is 0, 1, 2, 3 or 4;
• each R3 independently is halogen, cyano, hydroxy, amino, C1-4alkyl;
• C1-4halogenalkyl;
• C1-4hydroxyalkyl;
• C1-4aminoalkyl;
• C1-4alkylamino-C1-4alkyl;
• di-(C1-4alkyl)amino-C1-4alkyl;
• C1-4alkoxy-C1-4alkyl;
• C2-4alkenyl;
• C2-4halogenalkenyl;
• C2-4alkinyl;
• C2-4halogenalkinyl;
• C1-4alkoxy;
• C1-4halogenalkoxy;
• C1-4alkyl-amino;
• di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;
• R4 is hydrogen, halogen, cyano, hydroxy, amino, C1-4alkyl;
• C1-4halogenalkyl;
• C1-4hydroxyalkyl;
• C1-4aminoalkyl;
• C1-4alkylamino-C1-4alkyl;
• di-(C1-4alkyl)amino-C1-4alkyl;
• C1-4alkoxy-C1-4alkyl;
• C2-4alkenyl;
• C2-4halogenalkenyl;
• C2-4alkinyl;
• C2-4halogenalkinyl;
• C1-4alkoxy;
• C1-4halogenalkoxy;
• C1-4alkyl-amino;
• di-(C1-4alkyl)amino or C3-6cycloalkyl, wherein one carbon atom of the C3-6cycloalkyl may be replaced by an oxygen atom and wherein the C3-6cycloalkyl may be attached directly to the ring system or via a C1-2alkylene or an oxygen;
• B1 is a five- to six-membered aromatic ring system, which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R7;
• each R7 independently is
• halogen, cyano, hydroxy, amino,
• C1-4alkyl;
• C1-4halogenalkyl;
• C1-4hydroxyalkyl;
• C1-4aminoalkyl;
• C1-4alkylamino-C1-4alkyl;
• di-(C1-4alkyl)amino-C1-4alkyl;
• C1-4alkoxy-C1-4alkyl;
• C2-4alkenyl;
• C2-4halogenalkenyl;
• C2-4alkinyl;
• C2-4halogenalkinyl;
• C1-4alkoxy;
• C1-4alkoxy-C1-4alkoxy C1-4halogenalkoxy;
• C1-4alkyl-amino;
• di-(C1-4alkyl)amino;
• C1-4alkoxycarbonyl;
• or a three- to seven-membered monocyclic ring system which may be aromatic, saturated or unsaturated non-aromatic and which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R8;
• each R8 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy;
• or two R8 at the same ring atom together are oxo;
• or two R7 at adjacent ring atoms atoms form together with said ring atoms a fused five- to seven-membered monocyclic unsaturated non-aromatic ring system which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, wherein the ring system may in turn be substituted once or more than once by R9;
• each R9 independently is halogen, hydroxy, cyano, C1-4alkyl, C1-4halogenalkyl, C1-4alkoxy, or C1-4halogenalkoxy;
• or two R9 at the same ring atom together are oxo.